Variant chr21-25639776-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_021219.4(JAM2):c.-46C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 1,425,876 control chromosomes in the GnomAD database, including 2,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.054 ( 247 hom., cov: 32)

Exomes 𝑓: 0.055 ( 2135 hom. )

Consequence

JAM2
NM_021219.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.454

Variant links:

Genes affected

JAM2 (HGNC:14686): (junctional adhesion molecule 2) This gene belongs to the immunoglobulin superfamily, and the junctional adhesion molecule (JAM) family. The protein encoded by this gene is a type I membrane protein that is localized at the tight junctions of both epithelial and endothelial cells. It acts as an adhesive ligand for interacting with a variety of immune cell types, and may play a role in lymphocyte homing to secondary lymphoid organs. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2012]

JAM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 21-25639776-C-A is Benign according to our data. Variant chr21-25639776-C-A is described in ClinVar as [Benign]. Clinvar id is 1258951.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
JAM2	NM_021219.4 linkuse as main transcript	c.-46C>A	5_prime_UTR_variant	1/10	ENST00000480456.6
JAM2	NM_001270407.2 linkuse as main transcript	c.-46C>A	5_prime_UTR_variant	1/9
JAM2	NM_001270408.2 linkuse as main transcript	c.-46C>A	5_prime_UTR_variant	1/10
JAM2	NR_072999.2 linkuse as main transcript	n.519C>A	non_coding_transcript_exon_variant	1/10

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAM2	ENST00000480456.6 linkuse as main transcript	c.-46C>A	5_prime_UTR_variant	1/10	1	NM_021219.4	P1	P57087-1
JAM2	ENST00000400532.5 linkuse as main transcript	c.-46C>A	5_prime_UTR_variant	1/10	1			P57087-3
JAM2	ENST00000312957.9 linkuse as main transcript	c.-46C>A	5_prime_UTR_variant	1/9	2			P57087-2

Frequencies

GnomAD3 genomes

AF:

0.0544

AC:

8275

AN:

152068

Hom.:

246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0526

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0617

Gnomad ASJ

AF:

0.0785

Gnomad EAS

AF:

0.00871

Gnomad SAS

AF:

0.0354

Gnomad FIN

AF:

0.0523

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0581

Gnomad OTH

AF:

0.0517

GnomAD3 exomes

AF:

0.0560

AC:

7734

AN:

138168

Hom.:

263

AF XY:

0.0549

AC XY:

4122

AN XY:

75150

show subpopulations

Gnomad AFR exome

AF:

0.0488

Gnomad AMR exome

AF:

0.0872

Gnomad ASJ exome

AF:

0.0826

Gnomad EAS exome

AF:

0.00439

Gnomad SAS exome

AF:

0.0365

Gnomad FIN exome

AF:

0.0547

Gnomad NFE exome

AF:

0.0582

Gnomad OTH exome

AF:

0.0564

GnomAD4 exome

AF:

0.0549

AC:

69976

AN:

1273692

Hom.:

2135

Cov.:

AF XY:

0.0542

AC XY:

34339

AN XY:

633646

show subpopulations

Gnomad4 AFR exome

AF:

0.0490

Gnomad4 AMR exome

AF:

0.0827

Gnomad4 ASJ exome

AF:

0.0781

Gnomad4 EAS exome

AF:

0.0226

Gnomad4 SAS exome

AF:

0.0366

Gnomad4 FIN exome

AF:

0.0527

Gnomad4 NFE exome

AF:

0.0566

Gnomad4 OTH exome

AF:

0.0497

GnomAD4 genome

AF:

0.0544

AC:

8279

AN:

152184

Hom.:

247

Cov.:

AF XY:

0.0549

AC XY:

4084

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0525

Gnomad4 AMR

AF:

0.0617

Gnomad4 ASJ

AF:

0.0785

Gnomad4 EAS

AF:

0.00873

Gnomad4 SAS

AF:

0.0363

Gnomad4 FIN

AF:

0.0523

Gnomad4 NFE

AF:

0.0581

Gnomad4 OTH

AF:

0.0531

Alfa

AF:

0.0549

Hom.:

Bravo

AF:

0.0555

Asia WGS

AF:

0.0400

AC:

142

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over